O-Desmethyltramadol

O-Desmethyltramadol

Clinical data
Routes of administration	Converted Metabolite
Pharmacokinetic data
Metabolism	CYP2D6
Biological half-life	~ 9 h
Identifiers
IUPAC name 3-(2-((dimethylamino)methyl)-1-hydroxycyclohexyl)phenol
CAS Number	80456-81-1 N
PubChem (CID)	130829
ChemSpider	115703 Y
UNII	2WA8F50C3F N
ChEMBL	CHEMBL1400 N
Chemical and physical data
Formula	C15H23NO2
Molar mass	249.349 g/mol
3D model (Jmol)	Interactive image
SMILES OC2(c1cc(O)ccc1)CCCCC2CN(C)C
InChI InChI=1S/C15H23NO2/c1-16(2)11-13-6-3-4-9-15(13,18)12-7-5-8-14(17)10-12/h5,7-8,10,13,17-18H,3-4,6,9,11H2,1-2H3 Y Key:UWJUQVWARXYRCG-UHFFFAOYSA-N Y
NY (what is this?)

O-Desmethyltramadol (O-DSMT) is an opioid analgesic and the main active metabolite of tramadol. (+)-O-DSMT is the most important metabolite of tramadol produced in the liver after tramadol is consumed. Tramadol is demethylated by the liver enzyme CYP2D6 in the same way as codeine, and so similarly to the variation in effects seen with codeine, individuals who have a less active form of CYP2D6 ("poor metabolisers") will tend to get reduced analgesic effects from tramadol. This also results in a ceiling effect (dependent on CYP2D6 availability) which limits tramadol's range of therapeutic benefits to the treatment of moderate pain.

O-DSMT is considerably more potent as a μ opioid agonist compared to tramadol. Additionally, unlike tramadol, it is a high-affinity ligand of the δ- and κ-opioid receptors.

The two enantiomers of O-DSMT show quite distinct pharmacological profiles; both (+) and (−)-O-DSMT are inactive as serotonin reuptake inhibitors, but (−)-O-DSMT retains activity as a norepinephrine reuptake inhibitor, and so the mix of both the parent compound and metabolites contributes significantly to the complex pharmacological profile of tramadol. While the multiple receptor targets can be beneficial in the treatment of pain (especially complex pain syndromes such as neuropathic pain), it increases the potential for drug interactions compared to other opioids, and may also contribute to side effects.

O-DSMT has recently been marketed as a currently legal substitute for illegal opioid drugs, either in powder form or mixed into various other preparations. One such blend sold under the brand Krypton and containing powdered kratom leaf (Mitragyna speciosa) laced with O-DSMT was reportedly linked to at least 9 accidental deaths from overdose during 2010–2011.